Hydrogels are three-dimensional polymer networks capable of swelling in excess aqueous solution. Stimuli-responsive hydrogels, or “smart hydrogels”, undergo large changes in volume in response to physical or chemical changes in their environment. A number of hydrogels have been developed that are responsive to changes in pH, ionic strength, biochemicals, solvents, temperature, electric and magnetic field and light. Tanaka, Phase transitions of gels in Polyelectrolyte Gels: Properties, Preparation, and Applications, 480 ACS Symposium Series (1992). They have important applications as biomaterials, such as contact lenses, soft tissue prostheses and controlled delivery systems for drugs. Furthermore, applications of stimuli-responsive hydrogels include mechanochemical transducers that can be used as switches, microactuators, and as a type of artificial muscle. Although the number and diversity of existing hydrogels are impressive, they have been developed using a relatively small number of polymers and their derivatives, and conventional methods of chemical or physical crosslinking agents. Their functions and biocompatibility are often compromised since their structures are not well defined.
Proteins are becoming increasingly important because of their biological properties. Water-soluble polymers have been crosslinked with molecules of biological origin, such as oligopeptides, oligodeoxyribonucleotides, or intact native proteins. Subr, V. et al. Release of macromolecules and daunomycin from hydrophilic gels containing enzymatically degradable bonds. 1 J. Biomater. Sci. Edn, 261–278 (1990); Obaidat, A. A. & Park, K. Characterization of glucose dependent gel-sol phase transition of the polymeric glucose-concanavalin A hydrogel system. 13 Pham. Res. 989–995 (1996) However, very often there are several factors limiting and influencing the relationship between structure and properties of the hydrogel system, making it difficult to engineer hydrogels with specified responses to particular stimuli.
Bio-engineering techniques provide the ability to modify or synthesize proteins by means of genetic engineering to provide peptide sequences exhibiting desired biological or pharmacological properties as well as having desired physical characteristics due to their coiled or folding nature. Rapidly developing genetic engineering technology makes it possible to produce protein domain-based biomaterials with exact control over their structures through manipulating the DNA sequence encoding the protein structure.
Therefore, it is a significant advance in the art of hydrogels to provide a method to vastly increase the inventory of materials available for rational design of hydrogels. It is also highly desirable to provide a class of hydrogels having material characteristics such as viscosity, gelation temperature, swelling, elasticity, rigidity, porosity, biodegradability, bioerosion that can be precisely controlled and that are responsive to chemical and/or physical stimuli such as pH, temperature, and ionic strength.
This application provides such hydrogels by combining common synthetic polymers crosslinked by protein domains. Protein domains are a class of polypeptides or units of protein structure which are independently and stably folded structure. By manipulating the type, number, and arrangement of protein domains crosslinking the water soluble polymers, it is possible to control the mechanical properties of the hydrogel, such as strength and elasticity; or to give the gel new, or more pronounced, or controlled responses to environmental stimuli. In addition, by adjusting the amino acid sequence of the cross linking protein domains, it is possible to fine-tune the material properties of the gel for specific applications.